The people who knew the trial best had already put it in writing, twice, that they could not tell whether the drug worked.
That is the fact sitting underneath the accelerated approval the FDA granted on August 6 to Tudriqev, Replimune’s genetically modified herpes virus, given with the checkpoint drug nivolumab for patients whose advanced melanoma has stopped responding to standard immunotherapy. The agency’s own scientists had reviewed the evidence and turned it down, not once but twice, in July 2025 and again this past April. Both times the objection was the same, and it was not a small one.
The evidence behind Tudriqev is a single trial called IGNYTE, and IGNYTE is not the kind of study that usually clears the bar. It is a phase 1/2, open-label, single-arm study: no control group, no comparison arm, no randomization. Everyone in it got the drug, and the company counted how many tumors shrank. Of 140 patients enrolled, the efficacy math rested on the 91 who had at least one lesion the virus was never injected into. Among that group, 24.2 percent responded, with a confidence interval running from 15.8 to 34.3 percent, and the median response lasted 14.1 months.
That is a real signal for a subset of desperately sick people, and no honest reading pretends otherwise. But a single-arm trial cannot tell you what those same patients would have done on something else, or on nothing, and it tells you even less when the patients are a mixed bag to begin with. In its first rejection letter the FDA wrote that IGNYTE was not an “adequate and well-controlled clinical investigation,” and that its results “cannot be adequately interpreted due to the heterogeneity of the patient population.” Stripped of the regulatory register: the reviewers looked at the response numbers and said they could not tell what those numbers meant. The second letter, nine months later, said it again. The trial design was the reason both times.
By this summer the dispute had a venue. On July 30 the FDA convened its Cellular, Tissue, and Gene Therapies Advisory Committee on one question: were the IGNYTE efficacy results evaluable and clinically meaningful, or not. Going in, the agency’s staff were not coy about where they stood, calling a survival analysis the company had presented “not interpretable”, which is about the harshest thing a reviewer can say short of alleging you made it up. The panel heard all of it and voted 10 to 3 in the company’s favor, concluding, in the reporting from the room, that there was a large enough signal of efficacy and that patients were in urgent need of new options. A week later the approval followed.
Read the timeline slowly, because it repays a second look. No new randomized trial had been run and no new patients enrolled between the second rejection and the vote. The survival analysis Replimune brought to the table was the very one the agency’s reviewers called uninterpretable, and the heterogeneous population they said made the data unreadable in 2025 was the identical population in 2026. The evidence did not change. The verdict did.
Accelerated approval is the mechanism that makes this legal, and it is worth being precise about what it buys. It lets the FDA clear a drug on a “surrogate” measure, here the tumor-response rate, before anyone has shown patients live longer or better. The proof of actual benefit is pushed to a confirmatory trial that runs after the drug is already on the market and already being sold. For Tudriqev that trial is IGNYTE-3, a randomized phase 3 study comparing the combination against a physician’s choice of PD-1 therapy or chemotherapy, the control arm the first trial never had. It is not expected to read out until late 2027. In the meantime the therapy carries a list price of roughly $450,000 for a course of treatment before rebates. One analyst has pegged peak annual sales at $618 million, with the Street consensus closer to $1 billion, assuming the confirmatory trial eventually confirms something. The commercial machinery does not wait for that answer.
None of which means the virus does nothing. For a patient whose melanoma has slipped past every checkpoint drug on the shelf, a one-in-four shot at a durable response is not nothing, and the reported side effects in IGNYTE ran relatively mild. That case, giving dying patients a plausible option, is the strongest argument the approval has, and it is a serious one.
It was also equally true in July 2025, when the agency said no. What changed between the rejections and the approval was not the science. It was the FDA’s willingness to overrule its own reviewers once a company pushed a third time and a panel handed it cover. The agency spent two years telling Replimune its evidence could not be interpreted. It has now told every patient, insurer, and oncologist in the country that the same evidence is good enough to bill against. Whatever standard those two rejection letters were defending, it is no longer possible to say what it was.
Sources
- FDA – accelerated approval of Tudriqev (vusolimogene oderparepvec-wtpg) for advanced melanoma (Aug. 6, 2026)
- FDA – oncology approval detail: IGNYTE design, ORR 24.2%, median DOR 14.1 months
- Pharmacy Times – “After 2 CRLs, FDA Approves Vusolimogene Oderparepvec With Nivolumab”; first rejection and the “adequate and well-controlled” language
- CancerNetwork – FDA issues second complete response letter for RP1/nivolumab, again citing trial design
- BioSpace – FDA briefing calls Replimune’s survival analysis “not interpretable” ahead of the advisory committee
- Replimune – CTGTAC votes 10-3 that IGNYTE efficacy is evaluable and clinically meaningful (July 30, 2026)
- STAT – FDA approves Replimune melanoma drug rejected twice; $450,000 price, IGNYTE-3 confirmatory trial
- BioPharma Dive – Replimune rebounds to win FDA approval; confirmatory trial comparator, late-2027 readout, analyst peak-sales estimates
- FierceBiotech – Replimune’s twice-rejected melanoma drug prevails at FDA adcomm